The goal this project is to restore vision to persons with degenerative diseases of the retina. The target patient population are currently living with very limited or no sight and include persons with retinitis pigmentosa (RP) and age---related macular degeneration (AMD). RP is an inherited disorder affecting approximately 100,000 people in the US that is typically diagnosed in adolescents and young adults. Approximately one---quarter of all persons with RP become legally blind in both eyes. AMD is a relatively common affliction, affecting approximately ten million Americans, and it is the leading cause of blindness in Americans 55 years and older. Early detection and treatment of macular degeneration may help reduce vision loss but does not restore vision. There are no treatments that can restore moderate--- to high---acuity vision to these persons. The present proposal comprises candidate selection experiments for a small---molecule therapeutic. Specifically, we propose making high purity batches of our candidate photoswitch compounds, formulate those compounds for delivery to the back of the eye, and complete a series of operant conditioning vision restoration efficacy studies in rat models of RP. Based on those results, we will select a single compound and formulation for thorough characterization in pharmacokinetic (PK) studies in rat and rabbit and in in vitro and in vivo safety studies. Successful completion of the presen project will allow us to have a fully informed pre---IND meeting with the FDA, raise monies from private sources to fund the IND---enabling GLP safety studies, file an IND, and initiate a Phase 1 clinical trial in the target patient population. Such a clinical trial will provide a clear indiction of the efficacy of the compound in man.